Facing the challenges of new melanoma-targeted therapies: Treatment of severe fevers associated with dabrafenib/trametinib combination therapy

Abstract

With the emergence of new oral therapies for metastatic melanoma to the market, as well as ongoing pre-marketing trials and special access schemes, it is important to keep up to date with the side effect profiles of these medications. A common side effect associated with the BRAF inhibitor dabrafenib is severe fever symptoms such as pyrexia and rigors/chills; however, treatment options are limited. We report a patient who was debilitated by severe pyrexia and rigors caused by dabrafenib used in combination with trametinib to treat metastatic melanoma, who was treated with low-dose steroids. To our knowledge, the use of prednisolone for the treatment and prevention of further dabrafenib-associated pyrexia is not published; however, it is a low risk and low cost option that was very effective in this case.

Keywords

Melanoma pyrexia BRAF inhibitor trametinib dabrafenib

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References

Chapman

Hauschild

Robert

. BRIM-3 study group. Improved survival with vemurafenib in melanoma with BRAF V600E mutation. N Engl J Med 2011; 364: 2507–2516.

Flaherty

Infante

Daud

. Combined BRAF and MEK Inhibition in Melanoma with BRAF V600 Mutations. N Engl J Med 2012; 367: 1694–1703.

Menzies

Long

Murali

. Dabrafenib and its potential for the treatment of metastatic melanoma. Drug Des Devel Ther 2012; 6: 391–405.

Hauschild

Grob

Demidov

. Dabrafenib in BRAF-mutated metastatic melanoma: a multicentre, open-label, phase 3 randomised controlled trial. Lancet 2012; 380: 358–365.

Hauschild A, Grob JJ, Demidov LV, et al. Phase III, randomized, open-label, multicenter trial (BREAK-3) comparing the BRAF kinase inhibitor dabrafenib (GSK2118436) with dacarbazine (DTIC) in patients with BRAFV600E-mutated melanoma. J Clin Oncol 2012; 30(suppl): abstract LBA8500.

European Organisation for Research and Treatment of Cancer. Common Toxicity Criteria (CTC). EORTC, www.eortc.be (accessed 19 September 2013).

Dinarello

. Thermoregulation and the pathogenesis of fever. Infect Dis Clin North Am 1996; 10: 433–433.

Schwiebert

Beck

Stellato

. Glucocorticosteroid inhibition of cytokine production: relevance to antiallergic actions. J Allergy Clin Immunol 1996; 97: 143–152.

Patel

Suciu

Mortier

. EORTC Melanoma group. Extended schedule, escalated dose temozolomide versus dacarbazine in stage IV melanoma: final results of a randomised phase III study (EORTC 18032). Eur J Cancer 2011; 47: 1476–1483.